The objectives of this study are two-fold: one is to examine the potential neurotoxicity of chronic systemic intoxication with small amounts of acrylamide; the other to determine the role of local nerve exposure to acrylamide in producing dying-back neuropathy. For the first part, the clinical course of monkeys, daily intoxicated with minute amounts of acrylamide, will be followed for perioids up to two years. At intervals, Pacinian corpuscles will be biopsied and examined ultrastructurally. Upon completion of intoxication, monkeys will be perfused with fixative, and the nervous system will be examined by light and electron microscopy (EM). Results of this experiment will permit us to determine if present use of acrylamide, and its deployment as a contaminant of water-soluble polymers, creates an industrial hazard and is a potential environmental pollutant. The second part of the proposed work will begin by examining the effect of prolonged dermal contact of acrylamide to the feet of monkeys maintained in chairs. The strategy here is to determine the local toxic action of acrylamide on nerves. Other experiments are designed to test the importance of local toxicity in producing the dying-back pattern of nerve pathology, the indelible stamp of systemic acrylamide intoxication. For this facet of the study, acrylamide will be applied focally to short lengths of tibial nerves of cats by means of acrylamide-impregnanted Silastic nerve cuffs. These loci will be examined by EM, and the observation and measurement of the lengths of nodal gasp of single nerve fibers isolating testing. Nerve pathology produced under cuffs applied to proximal portions of the tibial nerves of monkeys will be statistically compared to pathology beneath more distally-applied nerve cuffs in systemically intoxicated animals prior to evidence of peripheral neuropathy, and unintoxicated animals. Results of these experiments are anticipated to bear heavily on our understanding of the mechanism by which acrylamide produces dying-back disease of the nervous system.